Is ABCG8 p.Ala548= (c.1644C>T) pathogenic?

ABCG8 p.Ala548= (c.1644C>T) is classified Likely benign in ABCG8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-24). Very rare (popmax 0.00878%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ABCG8 p.Ala548= (c.1644C>T)?

ABCG8 p.Ala548= (c.1644C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCG8 p.Ala548= (c.1644C>T) in the general population?

ABCG8 p.Ala548= (c.1644C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

ABCG8 p.Ala548=

c.1644C>T · rs200018072 · VCV1777107

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -2.9
Overall
CADD	5.285	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,086 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00273% 44/1,614,180 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,386
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,019
European (non-Finnish)	0.00263%	38,066
East Asian	0.00223%	44,876
Remaining individualsnot grpmax-eligible	0.0016%	62,502

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCG8
Protein: p.Ala548=
Coding: c.1644C>T
MANE Select: NM_022437
dbSNP: rs200018072
Type: single nucleotide variant
Location: chr2:43875301 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.94 · 8 PDB
Residue 548: the abc transmembrane type-2 domain; an α-helix

Full ABCG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCG8 p.Ala548Val Uncertain significance ★★ ⚠ same residue
ABCG8 p.Ala548Ser Uncertain significance ★ ⚠ same residue
ABCG8 p.Ala548Thr Uncertain significance ★ ⚠ same residue
ABCG8 p.Arg121Ter Pathogenic ★★ same condition
ABCG8 p.Arg405Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCG8 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG8 p.Ala248Thr Uncertain significance ★★ ⚠ same condition
ABCG8 p.Ala346Thr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcg8-p-ala548 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown